340-06-7Relevant articles and documents
Co-immobilized Phosphorylated Cofactors and Enzymes as Self-Sufficient Heterogeneous Biocatalysts for Chemical Processes
Velasco-Lozano, Susana,Benítez-Mateos, Ana I.,López-Gallego, Fernando
, p. 771 - 775 (2017)
Enzyme cofactors play a major role in biocatalysis, as many enzymes require them to catalyze highly valuable reactions in organic synthesis. However, the cofactor recycling is often a hurdle to implement enzymes at the industrial level. The fabrication of heterogeneous biocatalysts co-immobilizing phosphorylated cofactors (PLP, FAD+, and NAD+) and enzymes onto the same solid material is reported to perform chemical reactions without exogeneous addition of cofactors in aqueous media. In these self-sufficient heterogeneous biocatalysts, the immobilized enzymes are catalytically active and the immobilized cofactors catalytically available and retained into the solid phase for several reaction cycles. Finally, we have applied a NAD+-dependent heterogeneous biocatalyst to continuous flow asymmetric reduction of prochiral ketones, thus demonstrating the robustness of this approach for large scale biotransformations.
Use of hydrophobic bacterium Rhodococcus rhodochrous NBRC15564 expressed thermophilic alcohol dehydrogenases as whole-cell catalyst in solvent-free organic media
Hibino, Aiko,Ohtake, Hisao
, p. 838 - 843 (2013)
The hydrophobic bacterium Rhodococcus rhodochrous NBRC15564 was employed as a whole-cell biocatalyst to examine its potential for bioconversion in solvent-free organic media. The genes encoding two different thermostable alcohol dehydrogenases (ADHTt1 and ADHTt2) of Thermus thermophilus HB27 were expressed in R. rhodochrous cells. To inactivate indigenous mesophilic enzymes in R. rhodochrous, transformant cells were heated at 70 C for 10 min. Heat-treated hydrophobic wet cells were used for the bioconversion of 2,2,2-trifluoroacetophenone (TFAP) to α-(trifluoromethyl) benzyl alcohol (TFMBA) as a model reaction with ADHTt1. NADH, which was supplied in aqueous solution, was regenerated by converting cyclohexanol to cyclohexanone by ADHTt2. All reactions were performed by suspending heat-treated cells in solvent-free organic media consisting of 3.7 M TFAP and 4.8 M cyclohexanol (1:1, v/v ratio) at 60 C. When 800 mg heat-treated R. rhodochrous cells were dispersed in 2 mL of solvent-free organic media (400 mg cells/mL), the product concentration reached about 3.6 M TFMBA by 48 h with a total NADH turnover number of approximately 900. The overall productivity was 190 mol TFMBA/kg cells/h.
Assessment of headspace solid-phase microextraction (HS-SPME) for control of asymmetric bioreduction of ketones by Alternaria alternata
Ogórek, Rafa?,Jarosz, Bogdan
, p. 75 - 80 (2019/11/03)
The aim of this study was to assess the effectiveness of headspace solid-phase microextraction (HS-SPME) compared to liquid–liquid extractions using with methylene chloride (CH2Cl2) for control of fungal biotransformation of ketones of varying volatility. The proposed method was successfully applied. The best way to extract all the components of the mixture (alcohols, aldehydes) in quantities similar to the extraction of methylene chloride was the use of fibres coated with a combination of nonpolar material. SPME fibre assembly polydimethylsiloxane/divinylbenzene (PDMS/DVB) was most suitable for the extraction of the products mixture obtained after biotransformation of acetylcyclohexane and acetophenone. On the other hand, the best results were obtained for 2-acetylthiophene, α,α,α-trifluoroacetophenone and their derivatives using divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) fibre. In addition, our study showed that Alternaria alternata is a good biocatalyst for bioreduction of ketones to alcohols according to Prelog's rule.
Asymmetric transfer hydrogenation of ketones promoted by manganese(I) pre-catalysts supported by bidentate aminophosphines
Azouzi, Karim,Bruneau-Voisine, Antoine,Vendier, Laure,Sortais, Jean-Baptiste,Bastin, Stéphanie
, (2020/05/19)
A series of commercially available chiral amino-phosphines, in combination with Mn(CO)5Br, has been evaluated for the asymmetric reduction of ketones, using isopropanol as hydrogen source. With the most selective ligand, the corresponding manga
C1-Symmetric PNP Ligands for Manganese-Catalyzed Enantioselective Hydrogenation of Ketones: Reaction Scope and Enantioinduction Model
Zeng, Liyao,Yang, Huaxin,Zhao, Menglong,Wen, Jialin,Tucker, James H. R.,Zhang, Xumu
, p. 13794 - 13799 (2020/11/30)
A family of ferrocene-based chiral PNP ligands is reported. These tridentate ligands were successfully applied in Mn-catalyzed asymmetric hydrogenation of ketones, giving high enantioselectivities (92%～99% ee for aryl alkyl ketones) as well as high efficiencies (TON up to 2000). In addition, dialkyl ketones could also be hydrogenated smoothly. Manganese intermediates that might be involved in the catalytic cycle were analyzed. DFT calculation was carried out to help understand the chiral induction model. The Mn/PNP catalyst could discriminate two groups with different steric properties by deformation of the phosphine moiety in the flexible 5-membered ring.
A Hammett Study of Clostridium acetobutylicum Alcohol Dehydrogenase (CaADH): An Enzyme with Remarkable Substrate Promiscuity and Utility for Organic Synthesis
Berkowitz, David B.,Kudalkar, Gaurav P.,Lee, Joshua D.,Tiwari, Virendra K.
supporting information, p. 237 - 247 (2020/02/18)
Described is a physical organic study of the reduction of three sets of carbonyl compounds by the NADPH-dependent enzyme Clostridium acetobutylicum alcohol dehydrogenase (CaADH). Previous studies in our group have shown this enzyme to display broad substrate promiscuity, yet remarkable stereochemical fidelity, in the reduction of carbonyl compounds, including α-, β- and γ-keto esters (d -stereochemistry), as well as α,α-difluorinated-β-keto phosphonate esters (l -stereochemistry). To better mechanistically characterize this promising dehydrogenase enzyme, we report here the results of a Hammett linear free-energy relationship (LFER) study across three distinct classes of carbonyl substrates; namely aryl aldehydes, aryl β-keto esters and aryl trifluoromethyl ketones. Rates are measured by monitoring the decrease in NADPH fluorescence at 460 nm with time across a range of substrate concentrations for each member of each carbonyl compound class. The resulting v 0 versus [S] data are subjected to least-squares hyperbolic fitting to the Michaelis-Menton equation. Hammett plots of log(V max) versus σ X yield the following Hammett parameters: (i) for p -substituted aldehydes, ρ = 0.99 ± 0.10, ρ = 0.40 ± 0.09; two domains observed, (ii) for p -substituted β-keto esters ρ = 1.02 ± 0.31, and (iii) for p -substituted aryl trifluoromethyl ketones ρ = -0.97 ± 0.12. The positive sign of ρ indicated for the first two compound classes suggests that the hydride transfer from the nicotinamide cofactor is at least partially rate-limiting, whereas the negative sign of ρ for the aryl trifluoromethyl ketone class suggests that dehydration of the ketone hydrate may be rate-limiting for this compound class. Consistent with this notion, examination of the 13 C NMR spectra for the set of p -substituted aryl trifluo romethyl ketones in 2percent aqueous DMSO reveals significant formation of the hydrate (gem -diol) for this compound family, with compounds bearing the more electron-withdrawing groups showing greater degrees of hydration. This work also presents the first examples of the CaADH-mediated reduction of aryl trifluoromethyl ketones, and chiral HPLC analysis indicates that the parent compound α,α,α-trifluoroacetophenone is enzymatically reduced in 99percent ee and 95percent yield, providing the (S)-stereoisomer, suggesting yet another compound class for which this enzyme displays high enantioselectivity.
Asymmetric Catalytic Meerwein-Ponndorf-Verley Reduction of Ketones with Aluminum(III)-VANOL Catalysts
Guan, Yong,Mohammadlou, Aliakbar,Staples, Richard,Sullivan, Ryan P.,Wulff, William D.,Yin, Xiaopeng,Zheng, Li
, p. 7188 - 7194 (2020/07/21)
We report herein an efficient aluminum-catalyzed asymmetric MPV reduction of ketones with broad substrate scope and excellent yields and enantiomeric inductions. A variety of aromatic (both electron-poor and electron-rich) and aliphatic ketones were converted to chiral alcohols in good yields with high enantioselectivities (26 examples, 70-98percent yield and 82-99percent ee). This method operates under mild conditions (-10 °C) and low catalyst loading (1-5 mol percent). Furthermore, this process is catalyzed by the earth-abundant main-group element aluminum and employs 2-propanol as the hydride source.
Asymmetric Synthesis of Primary and Secondary β-Fluoro-arylamines using Reductive Aminases from Fungi
González-Martínez, Daniel,Cuetos, Aníbal,Sharma, Mahima,García-Ramos, Marina,Lavandera, Iván,Gotor-Fernández, Vicente,Grogan, Gideon
, p. 2421 - 2425 (2020/03/25)
The synthesis of chiral amines is of central importance to pharmaceutical chemistry, and the inclusion of fluorine atoms in drug molecules can both increase potency and slow metabolism. Optically enriched β-fluoroamines can be obtained by the kinetic resolution of racemic amines using amine transaminases (ATAs), but yields are limited to 50 %, and also secondary amines are not accessible. In order to overcome these limitations, we have applied NADPH-dependent reductive aminase enzymes (RedAms) from fungal species to the reductive amination of α-fluoroacetophenones with ammonia, methylamine and allylamine as donors, to yield β-fluoro primary or secondary amines with >90 % conversion and between 85 and 99 % ee. In addition, the effect of the progressive introduction of fluorine atoms to the α-position of the acetophenone substrate reveals the effect of mono-, di- and tri-fluorination on the proportion of amine and alcohol in product mixtures, shedding light on the promiscuous ability of imine reductase (IRED)-type dehydrogenases to reduce fluorinated acetophenones to alcohols.
Highly Enantioselective Transfer Hydrogenation of Prochiral Ketones Using Ru(II)-Chitosan Catalyst in Aqueous Media
Sz?ll?si, Gy?rgy,Kolcsár, Vanessza Judit
, p. 820 - 830 (2018/12/13)
Unprecedentedly high enantioselectivities are obtained in the transfer hydrogenation of prochiral ketones catalyzed by a Ru complex formed in situ with chitosan chiral ligand. This biocompatible, biodegradable chiral polymer obtained from the natural chitin afforded good, up to 86 % enantioselectivities, in the aqueous-phase transfer hydrogenation of acetophenone derivatives using HCOONa as hydrogen donor. Cyclic ketones were transformed in even higher, over 90 %, enantioselectivities, whereas further increase, up to 97 %, was obtained in the transfer hydrogenations of heterocyclic ketones. The chiral catalyst precursor prepared ex situ was examined by scanning electron microscopy, FT-mid- and -far-IR spectroscopy. The structure of the in situ formed catalyst was investigated by 1H NMR spectroscopy and using various chitosan derivatives. It was shown that a Ru pre-catalyst is formed by coordination of the biopolymer to the metal by amino groups. This precursor is transformed in water insoluble Ru-hydride complex following hydrogen donor addition. The practical value of the developed method was verified by preparing over twenty chiral alcohols in good yields and optical purities. The catalyst was applied for obtaining optically pure chiral alcohols at gram scale following a single crystallization.
Chiral (cyclopentadienone)iron complexes with a stereogenic plane as pre-catalysts for the asymmetric hydrogenation of polar double bonds
Bai, Xishan,Cettolin, Mattia,Mazzoccanti, Giulia,Pierini, Marco,Piarulli, Umberto,Colombo, Valentina,Dal Corso, Alberto,Pignataro, Luca,Gennari, Cesare
, p. 1415 - 1424 (2019/02/09)
In this paper, we describe a small library of easy-to-prepare chiral (cyclopentadienone)iron pre-catalysts for enantioselective C[dbnd]O and C[dbnd]N hydrogenations. Starting from readily accessible achiral materials, six chiral (cyclopentadienone)iron complexes (1a-f) possessing a stereogenic plane were synthesized in racemic form. Based on the screening of pre-catalysts (±)-1a-f in the hydrogenation of ketones and ketimines, we selected two complexes (1a and 1d) for resolution by semipreparative enantioselective HPLC. The absolute configuration of the separated enantiomers of 1a and 1d was assigned by XRD analysis (1a) and by comparison between experimental and DFT-calculated ECD and ORD spectra (1d). The enantiopure pre-catalysts (S)-1a and (R)-1d were tested in the asymmetric hydrogenation of several ketones and ketimines and showed good activity and modest enantioselectivity, the e.e. values ranging from very low to moderate (54%).
